Vancomycin heteroresistance is associated with reduced mortality in ST239 methicillin-resistant Staphylococcus aureus blood stream infections

Sebastiaan J van Hal, Mark Jones, Iain B Gosbell, David L Paterson, Sebastiaan J van Hal, Mark Jones, Iain B Gosbell, David L Paterson

Abstract

Background: Despite hVISA infections being associated with vancomycin treatment failure, no previous study has been able to detect a mortality difference between heteroresistant vancomycin intermediate Staphylococcus aureus (hVISA) and vancomycin susceptible Staphylococcus aureus (VSSA) bloodstream infections (BSI).

Methodology: Consecutive methicillin-resistant S. aureus (MRSA) BSI episodes between 1996 and 2008 were reviewed. Patient demographics, clinical presentation, treatment and overall mortality at 30 days were extracted from the medical records. All isolates underwent vancomycin minimum inhibitory concentration (VMIC) testing by broth microdilution and Etest. hVISA was confirmed by population analysis profiling using the area under the curve method (PAP-AUC).

Principal findings: 401 evaluable MRSA BSI episodes were identified over the 12 years. Of these, 46 (11.5%) and 2 (0.5%) were confirmed as hVISA and VISA by PAP-AUC respectively. hVISA predominantly occurred in ST239-like MRSA isolates with high VMIC (2 mg/L). Compared to VSSA, hVISA was associated with chronic renal failure (p<0.001), device related infections (haemodialysis access) (p<0.001) and previous vancomycin usage (p = 0.004). On multivariate analysis, independent predictors of mortality included age, presence of multiple co-morbidities, principal diagnosis, transit to ICU and severity of illness while infection related surgery and hVISA phenotype were associated with increased survival.

Conclusions/significance: The presence of hVISA is dependent on the appropriate interplay between host and pathogen factors. hVISA in ST239 MRSA is an independent predictor of survival. Whether these findings would be replicated across all MRSA clones is unknown and warrants further study.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Kaplan Meyer survival curves 30…
Figure 1. Kaplan Meyer survival curves 30 days from the initial positive blood culture bottle for Methicillin-resistant Staphylococcus aureus.
Patients with vancomycin heteroresistance (hVISA) were significantly less likely to die compared to patients with vancomycin susceptible (VSSA) blood stream episodes (OR of 0.27; 95% CI 0.09–0.83; p = 0.022).

References

    1. Corey GR. Staphylococcus aureus bloodstream infections: definitions and treatment. Clin Infect Dis. 2009;48(Suppl 4):S254–259.
    1. Turnidge JD, Kotsanas D, Munckhof W, Roberts S, Bennett CM, et al. Staphylococcus aureus bacteraemia: a major cause of mortality in Australia and New Zealand. Med J Aust. 2009;191:368–373.
    1. Chua K, Howden BP. Treating Gram-positive infections: vancomycin update and the whys, wherefores and evidence base for continuous infusion of anti-Gram-positive antibiotics. Curr Opin Infect Dis. 2009;22:525–534.
    1. Hiramatsu K, Hanaki H, Ino T, Yabuta K, Oguri T, et al. Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. J Antimicrob Chemother. 1997;40:135–136.
    1. Hiramatsu K, Aritaka N, Hanaki H, Kawasaki S, Hosoda Y, et al. Dissemination in Japanese hospitals of strains of Staphylococcus aureus heterogeneously resistant to vancomycin. Lancet. 1997;350:1670–1673.
    1. Bae IG, Federspiel JJ, Miro JM, Woods CW, Park L, et al. Heterogeneous vancomycin-intermediate susceptibility phenotype in bloodstream methicillin-resistant Staphylococcus aureus isolates from an international cohort of patients with infective endocarditis: prevalence, genotype, and clinical significance. J Infect Dis. 2009;200:1355–1366.
    1. van Hal SJ, Paterson DL. Systematic Review and Meta-Analysis of the Significance of Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Isolates. Antimicrob Agents Chemother. 2011;55:405–410.
    1. Rybak MJ, Leonard SN, Rossi KL, Cheung CM, Sader HS, et al. Characterization of vancomycin-heteroresistant Staphylococcus aureus from the metropolitan area of Detroit, Michigan, over a 22-year period (1986 to 2007). J Clin Microbiol. 2008;46:2950–2954.
    1. Charles PG, Ward PB, Johnson PD, Howden BP, Grayson ML. Clinical features associated with bacteremia due to heterogeneous vancomycin-intermediate Staphylococcus aureus. Clin Infect Dis. 2004;38:448–451.
    1. Maor Y, Hagin M, Belausov N, Keller N, Ben-David D, et al. Clinical features of heteroresistant vancomycin-intermediate Staphylococcus aureus bacteremia versus those of methicillin-resistant S. aureus bacteremia. J Infect Dis. 2009;199:619–624.
    1. Neoh HM, Hori S, Komatsu M, Oguri T, Takeuchi F, et al. Impact of reduced vancomycin susceptibility on the therapeutic outcome of MRSA bloodstream infections. Ann Clin Microbiol Antimicrob. 2007;6:13.
    1. Musta AC, Riederer K, Shemes S, Chase P, Jose J, et al. Vancomycin MIC plus heteroresistance and outcome of methicillin-resistant Staphylococcus aureus bacteremia: trends over 11 years. J Clin Microbiol. 2009;47:1640–1644.
    1. Soriano A, Marco F, Martinez JA, Pisos E, Almela M, et al. Influence of vancomycin minimum inhibitory concentration on the treatment of methicillin-resistant Staphylococcus aureus bacteremia. Clin Infect Dis. 2008;46:193–200.
    1. Takesue Y, Nakajima K, Takahashi Y, Ichiki K, Ishihara M, et al. Clinical characteristics of vancomycin minimum inhibitory concentration of 2 mug/ml methicillin-resistant Staphylococcus aureus strains isolated from patients with bacteremia. J Infect Chemother 2010
    1. Howden BP, Smith DJ, Mansell A, Johnson PD, Ward PB, et al. Different bacterial gene expression patterns and attenuated host immune responses are associated with the evolution of low-level vancomycin resistance during persistent methicillin-resistant Staphylococcus aureus bacteraemia. BMC Microbiol. 2008;8:39.
    1. McCallum N, Karauzum H, Getzmann R, Bischoff M, Majcherczyk P, et al. In vivo survival of teicoplanin-resistant Staphylococcus aureus and fitness cost of teicoplanin resistance. Antimicrob Agents Chemother. 2006;50:2352–2360.
    1. Peleg AY, Monga D, Pillai S, Mylonakis E, Moellering RC, Jr, et al. Reduced susceptibility to vancomycin influences pathogenicity in Staphylococcus aureus infection. J Infect Dis. 2009;199:532–536.
    1. Horne KC, Howden BP, Grabsch EA, Graham M, Ward PB, et al. Prospective comparison of the clinical impacts of heterogeneous vancomycin-intermediate methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-susceptible MRSA. Antimicrob Agents Chemother. 2009;53:3447–3452.
    1. van Hal SJ, Paterson DL, Gosbell IB. The presence of vancomycin heteroresistance in methicillin-resistant Staphylococcus aureus blood stream infections is not associated with increased mortality. 2010. abstr. K290, p. Abstr 50th Interscience Conference Antimicrobial Agents and Chemotherapy, Boston, MA.
    1. Patel N, Pai MP, Rodvold KA, Lomaestro B, Drusano GL, et al. Vancomycin: We Can't Get There from Here. Clin Infect Dis. 2011;52:969–974.
    1. Howden BP, Davies JK, Johnson PD, Stinear TP, Grayson ML. Reduced vancomycin susceptibility in Staphylococcus aureus, including vancomycin-intermediate and heterogeneous vancomycin-intermediate strains: resistance mechanisms, laboratory detection, and clinical implications. Clin Microbiol Rev. 2010;23:99–139.
    1. van Hal SJ, Wehrhahn MC, Barbagiannakos T, Mercer J, Chen D, et al. Performance of Various Testing Methodologies for Detection of Heteroresistant Vancomycin-Intermediate Staphylococcus aureus in Bloodstream Isolates. J Clin Microbiol. 2011;49:1489–1494.
    1. Vikram HR, Buenconsejo J, Hasbun R, Quagliarello VJ. Impact of valve surgery on 6-month mortality in adults with complicated, left-sided native valve endocarditis: a propensity analysis. JAMA. 2003;290:3207–3214.
    1. Sakoulas G, Eliopoulos GM, Fowler VG, Jr, Moellering RC, Jr, Novick RP, et al. Reduced susceptibility of Staphylococcus aureus to vancomycin and platelet microbicidal protein correlates with defective autolysis and loss of accessory gene regulator (agr) function. Antimicrob Agents Chemother. 2005;49:2687–2692.
    1. Sakoulas G, Eliopoulos GM, Moellering RC, Jr, Wennersten C, Venkataraman L, et al. Accessory gene regulator (agr) locus in geographically diverse Staphylococcus aureus isolates with reduced susceptibility to vancomycin. Antimicrob Agents Chemother. 2002;46:1492–1502.
    1. Hidayat LK, Hsu DI, Quist R, Shriner KA, Wong-Beringer A. High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections: efficacy and toxicity. Arch Intern Med. 2006;166:2138–2144.
    1. Holmes N, Turnidge J, Korman T, Munckhof W, O'Sullivan M, et al. Increased mortality in patients with Staphylococcus aureus bacteraemia (SAB) with elevated vancomycin MIC regardless of antibiotic treatment. 2010. ISSSI Bath, United Kingdom, Proffered Paper.
    1. Moise PA, Sakoulas G, Forrest A, Schentag JJ. Vancomycin in vitro bactericidal activity and its relationship to efficacy in clearance of methicillin-resistant Staphylococcus aureus bacteremia. Antimicrob Agents Chemother. 2007;51:2582–2586.
    1. Sakoulas G, Moise-Broder PA, Schentag J, Forrest A, Moellering RC, Jr, et al. Relationship of MIC and bactericidal activity to efficacy of vancomycin for treatment of methicillin-resistant Staphylococcus aureus bacteremia. J Clin Microbiol. 2004;42:2398–2402.
    1. Jones RN. Microbiological features of vancomycin in the 21st century: minimum inhibitory concentration creep, bactericidal/static activity, and applied breakpoints to predict clinical outcomes or detect resistant strains. Clin Infect Dis. 2006;42(Suppl 1):S13–24.
    1. Clinical Laboratory Standards Institute (CLSI) Performance standards for antimicrobial susceptibility testing; sixteenth informational supplement. CLSI document M100-S20. Wayne, PA: CLSI; 2010.
    1. Walsh TR, Bolmstrom A, Qwarnstrom A, Ho P, Wootton M, et al. Evaluation of current methods for detection of staphylococci with reduced susceptibility to glycopeptides. J Clin Microbiol. 2001;39:2439–2444.
    1. Walsh TR, Howe RA, Wootton M, Bennett PM, MacGowan AP. Detection of glycopeptide resistance in Staphylococcus aureus. J Antimicrob Chemother. 2001;47:357–358.
    1. Lesens O, Methlin C, Hansmann Y, Remy V, Martinot M, et al. Role of comorbidity in mortality related to Staphylococcus aureus bacteremia: a prospective study using the Charlson weighted index of comorbidity. Infect Control Hosp Epidemiol. 2003;24:890–896.
    1. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control. 2008;36:309–332.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa